NEW JERSEY LYME DISEASE, BABESIA, ERLICHIA AND BARTONELLA AND TREATMENT

PART FOUR

A REVIEW OF MAJOR STUDIES

Recently a troubled and agitated New Jersey pseudo expert in Lyme disease seemed to report no interest in treating Babesia, and since her old protocols were questionable anyway, I suppose it was just as well. Others are treating her failures. She had one tool and one way to treat. In 2008 this is 1990's medicine. I believe one must read very widely, and just because past IV treatment has helped some patients does not mean one tool is the only option in the tool box.

So let's look at a small sample of the PUBLISHED DATA on New Jersey. But as real researchers and seasoned clinicians know, the best information is not even published yet. This is one reason to have expert clinicians and researchers to be close and talking back and forth. I recall one article I wrote for the Journal of the American Medical Association which was accepted and yet was not published for a year. In tick and flea-infection science at this time, a year is 10 years.

Here are some sample material relating only to New Jersey Lyme Disease

Cat-scratch disease is one of several diseases known to be caused by Bartonella species. Some infections due to Bartonella resolve spontaneously without treatment with antibiotics, but in other cases the disease can be fatal without treatment. This case study reports a 7-year-old male who presented with an unexplained encephalopathy and unusual retinal findings associated with evidence supporting infection by B. henselae. The 7-year-old male presented with a 2-week history of general malaise and cervical lymphadenopathy progressing onto fever, headache, vomiting, and confusion associated with meningism. Lumbar puncture revealed a raised cerebrospinal fluid protein, low glucose, and raised white cell count. Abnormal retinal findings and raised antibodies titres to B. quintana indicated a diagnosis of cat-scratch disease. He was treated with azithromycin orally for 3 weeks and made a complete recovery.

Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA.

Cat-scratch disease resulting from Bartonella henselae infection is usually a benign, self-limited process in immunocompetent children. Even the rare cases associated with neurologic manifestations are not generally fatal. We report a case of a previously healthy 6-year-old boy with cat-scratch disease, systemic dissemination, and encephalitis that led to his death. Autopsy revealed perivascular lymphocytic infiltrates and microglial nodules in the brain. To our knowledge, this finding has not been previously reported in B. henselae infection, possibly because of the paucity of material available for complete neuropathologic evaluation. This case illustrates the extreme severity of the spectrum with which cat-scratch disease can present and provides evidence of brain histopathology that may be representative of the disease.

We describe a 16-month-old girl who suffered from encephalopathy leading to intensive care unit hospitalization, complicated by Guillain-Barre syndrome and hydrocephalus, and who had serologic and molecular evidence of central nervous system infection by B. quintana. The possible association of B. quintana with Guillain-Barre syndrome and hydrocephalus has not been previously described and demonstrates the growing spectrum of neurologic complications of Bartonella spp. infections.

Cat scratch disease (CSD) is a zoonotic illness caused by the Gram negative bacillus Bartonella henselae characterized by a small skin lesion at the site of a bite, lick or scratch by a cat, commonly followed by regional lymphadenopathy 1 or 2 weeks later. We report herein on severe neurological complications of CSD combining brainstem encephalopathy and basal ganglia impairment. This 12-year-old female acutely presented to a local hospital with profound coma and a prolonged tonic posturing of extremities. On the neurological examination she was deeply comatose with pin-point pupils and lack of vestibulo-ocular responses, suggestive of brainstem encephalopathy, along with marked rigid hypertonicity suggestive also of basal ganglia impairment. Initially suspecting Herpes simplex encephalitis or acute disseminated encephalomyelitis she was promptly started with high-dose methyl-prednisolone and acyclovir. Her parents apparently reported that she was scratched by a kitten some 4 weeks prior to her present admission and as such, suspecting CSD, she was begun with doxycycline and rifampicin. Her serology had proven positive for IgM antibodies to Bartonella henselae establishing the diagnosis. She regained consciousness after 4 days and the signs of brainstem and extra-pyramidal impairment also gradually abated and disappeared after 10 days. A follow-up exam after a month disclosed mild extra-pyramidal abnormalities which disappeared after 3 months. Although extremely rare, CSD should be also considered in a patient presenting with a severe encephalopathy and associated basal ganglia impairment. The prompt administration of high-dose methyl-prednisolone upon admission may have contributed to the favorable outcome in our patient and therefore should be advocated in any patient presenting with profound encephalopathy regardless the underlying etiology recovered later.

OBJECTIVE: To study the infection status of Bartonella spp. in rodents in western part of Yunnan province. METHODS: Blood samples were collected from four species of rodents captured in four counties in western Yunnan in 2004. Bartomella was isolated through being cultured in brain and heart infusion agar media containing 5% rabbit blood. Suspective Bartomella strains isolates were confirmed by amplification of 379 bp of citrate synthase (gltA) gene with specific primer by polymerase chin reaction (PCR). RESULTS: Fifty-four strains of Bartomella isolates were obtained from 397 samples including four rodent species captured in the fields with an overall isolation-rate of 13.6% (54/397). The rates of isolation among different species were: 22.0% (22/100) in Rattus nitidus, 14.8% (31/210) in Rattus flavipectus and 1.2%(1/87) in Rattus norvegicus while in R. t. yunnanensis it was negative. CONCLUSION: These findings demonstrated that the local rodents in western Yunnan were widely infected by Bartomella spp. It is indispensable to study the vector and the route of transmission to discover the relations between Bartomella and human diseases.

INTRODUCTION: Bartonella hensalae is a poorly known cause of encephalopathy in young subjects. OBSERVATION: A 17 year-old adolescent was admitted in a state of emergency because of frequent convulsive seizures and inter-critical drowsiness. The diagnosis of encephalopathy was made on the association of these clinical signs and electro-encephalographic abnormalities. The presence of a cat in his home, a right axillary lymph node that had appeared in a context of fever, and positive serological kinetics related this encephalopathy to a bartonellosis. The course was good. DISCUSSION: Diagnosis of a Bartonella hensalae encephalopathy is based on a range of anamnesic, clinical and microbiological arguments. The potential interest of antibiotic therapy and its modalities remains to be established.

Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

OBJECTIVE: To investigate Bartonella infections in small mammalian reservoir hosts from different environments and types of climate in Yunnan. METHODS: Femoral blood samples were collected from the anesthetic captured animals from five counties including three types of climate. All isolates were grown on brain and heart infusion agar plates containing 5% defibrinated rabbit blood. The agar plates were incubated at 35 degrees C in a humidified with 5% CO2 environment for at least 4 weeks. Bartonella-like isolates were confirmed by the polymerase chain reaction and visualizing the target gene fragment by gel electrophoresis. RESULTS: Bartonella species were isolated from 69 of 176 small animals including 4 species of 3 genera from 4 counties and the total prevalence in rodents was 39.2%. The maximal prevalence was 42.0% of Rattus tanezumi flavipectus usually inhabiting indoors and courtyard and contacting closely to human. Moreover, Bartonella isolates were obtained from Rattus noruegicus, Eothenomys miletus and Mus pahari. Life environments of captured animals involved indoors, courtyard, brush and forest in mountain. CONCLUSION: The finding in this study suggested the characteristic of diversity of Bartonella infections in rodent hosts in southern China included Bartonella species parasiting in a wide range of animal hosts in different environments as well as climate types. Further investigations were needed in different areas in China to confirm more mammalian reservoir hosts with Bartonella infections.

Cat scratch disease (CSD) is an infectious illness caused by a Gram-negative rod named Bartonella henselae. Typical CSD is characterized by a small skin lesion at the site of a scratch or a bite, followed by regional lymphadenopathy, one to two weeks later. Atypical forms may present as ocular manifestations, neurological manifestations, hepatosplenic involvement and vertebral osteomyelitis. Among neurological complications, encephalopathy is by far the most common. Other neurological manifestations are very rare. We report a case of an 11-year-old boy, with a posterior cervical lymphadenopathy and fever. Cat scratch disease was diagnosed and treated after a positive "Whartin-Starry" stain on lymph node biopsy. Two weeks after treatment, the patient was readmitted presenting an acute episode of left hemiplegia. A brain MRI demonstrated a right subcortical fronto-parietal lesion with no contrast enhancement. Complete recovery was observed after corticosteroid treatment.

Cat scratch disease (CSD) is a world-wide, diffuse, non-epidemic infection caused by the Gram-negative bacillus Bartonella henselae. The occurrence of encephalopathy represents an infrequent and atypical complication, whose manifestations include ischemic strokes, transverse myelitis and epileptic seizures. Status epilepticus has been described as the most frequent emergency in CSD encephalopathy. In this report, we describe a case of CSD complicated by an epilepsia partialis continua (EPC) manifested as rhythmic movements of the flexor muscles of the left hand. Although CSD is a benign, self-limited disease and a complete neurological recovery usually occurs, in the present case the EPC resulted in a partial epilepsy. Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and back-averaged EEG data recorded during myoclonic activity document this CSD complication.

Department of Neurology, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York, USA.

OBJECTIVE: To describe the epidemiologic, clinical, neuroimaging, and laboratory features; treatment; and outcome in a cohort of children with acute disseminated encephalomyelitis (ADEM). METHODS: A 6-year retrospective chart review of children with the diagnosis of ADEM was conducted. RESULTS: Eighteen cases were identified. Sixteen patients (88%) presented in either winter or spring. Thirteen children (72%) had a recent upper respiratory tract illness. Patients presented most often with motor deficits (77%) and secondly with altered consciousness (45%). Spinal fluid abnormalities occurred in 70%. Despite rigorous microbiologic testing, a definite microbiologic diagnosis was established only in 1 child with Epstein-Barr virus disease and probable or possible diagnoses in 3 children with Bartonella henselae, Mycoplasma pneumoniae, or rotavirus disease. Brain magnetic resonance imaging identified lesions in the cerebral cortex in 80%, in subcortical white matter in 93%, in periventricular white matter in 60%, in deep gray matter in 47%, and in brainstem in 47% of patients. Eleven patients (61%) were treated with corticosteroids, and 2 were treated with intravenous immunoglobulins. All patients survived. Three patients (17%) had long-term neurologic sequelae. CONCLUSIONS: Epidemiologic evidence from this study suggests an infectious cause for ADEM. The agent is most likely a difficult-to-diagnose winter/spring respiratory virus. Magnetic resonance imaging was the neuroimaging study of choice for establishing the diagnosis and for following the course of the disease. Prognosis for survival and outcome was excellent. Recurrent episodes of ADEM must be differentiated from multiple sclerosis.

Bacterial infection due to Bartonella henselae commonly develops in children and young adults following cat/dog contacts and/or cat/dog scratches. Regional lymphadenopathy is its most common clinical expression. However, encephalitis and Parinaud's syndrome (oculoglandular syndrome) have also been reported as has systemic illness. A review of the international literature in all languages revealed no fatal complications in immunocompetent hosts. A four-year-old white child with no underlying illness began to have seizure-like activity. She was taken to a local hospital and subsequently transferred to a medical center. The child was treated aggressively for seizures and fever of unknown origin. However, her condition rapidly declined and she died without a specific diagnosis. At autopsy there was marked cerebral edema with no gross evidence of acute meningitis. Microscopic exams revealed multiple granulomatous lesions as well as a meningitis and encephalitis. A variety of cultures and stains were negative for acid fast and fungal organisms. Warthin-Starry stains of involved tissue including brain and liver revealed pleomorphic rod shaped bacilli consistent with Barronella henselae. Analysis of brain tissue with polymerase chain reaction (PCR) and Southern blot for the deoxyribonucleic acid (DNA) was definitive for DNA of Bartonella henselae bacteria.

First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus.

We report an atypical case of cat scratch disease (CSD), accompanied with encephalopathy that is a rare complication of CSD. A 17-year old man consulted a doctor for his right axillary lymphadenopathy. The history of his contact with cats and the sign of lymphnode swelling and fever suggested a suspect of cat scratch disease. Administration of ampicillin improved his clinical symptoms, but a few days later he suddenly fell into coma after an episode of convulsion. The CT scan of the brain and laboratory tests showed no significant findings except the slightly elevated cell counts and concentration of protein in his cerebrospinal fluid. He was referred to our hospital on the next day for further examinations and treatments for his coma of unknown cause. The physical examination on admission revealed slight neck stiffening and hypertonicity of his right lower limb, but radiological and laboratory tests showed no significant findings. He gradually recovered from his coma without apparent sequelae in three weeks. Indirect fluorescence antibody titers for CSD in his serum showed a significant elevation to 1:160 of IgM and 1:512 of IgG, and his clinical features were compatible to these of CSD with complications of the central nervous system.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. Karen_Munana@ncsu.edu

Bartonella henselae is known to cause central nervous system (CNS) disease in humans, and neurological signs have been observed in experimentally infected cats. However, the pathogenesis of CNS disease remains unclear. This study was undertaken to determine whether B. henselae infects feline fetal brain cells in vitro. Microglial-cell- and astrocyte-enriched cultures were inoculated with B. henselae. GimŽnez staining identified bacterial organisms within microglial cells by day 7 postinoculation. The viability of the intracellular bacteria was demonstrated by incubating cultures with gentamicin and plating cell lysate on agar. Electron microscopy identified intracellular organisms with characteristic Bartonella morphology but identified no ultrastructural abnormalities within infected microglial cells. No evidence of infection was seen in Bartonella-inoculated astrocyte cultures. These findings suggest a role for microglia in the pathogenesis of B. henselae-associated neurological disease.

Most cases of Escherichia coli K1 meningitis arise as a result of haematogenous spread, however there is a limited understanding of the mechanisms by which circulating E. coli K1 cross the blood-brain barrier. We have previously shown that environmental growth conditions both positively and negatively influence the capabilities of E. coli K1 to invade brain microvascular endothelial cells (BMEC), for example growth in media supplemented with 50% newborn bovine serum (NBS) increased BMEC invasion, whereas growth in media supplemented with 0.2 M NaCl repressed invasion in vitro and in vivo. In this study, differential fluorescence induction (DFI) was used to identify E. coli K1 genes involved in this differentially expressed invasion phenotype. E. coli K1 promoter libraries were constructed and screened for gfp expression in a manner analogous to the above growth conditions. Twenty-four clones were isolated that showed fluorescence induction when grown under the invasion-enhancing condition (i.e. NBS). Four of these clones also demonstrated repression or no induction of fluorescence when grown under the invasion-repressing condition (i.e. 0.2 M NaCl). One such clone, containing a ygdP promoter and an open reading frame (ORF), showed significant homology to Bartonella bacilliformis IalA (invasion associated locus). Among the other NBS-inducing loci, finPtraJ was identified as well as several clones with no homology to other known genes. When ygdP, finPtraJ and several of the unique loci were disrupted in E. coli K1, there was a significant decrease in human BMEC (HBMEC) invasion. RNA transcript analysis determined that these newly identified invasion loci were differentially regulated at the transcriptional level. This is the first demonstration of using DFI to identify E. coli K1 genes contributing to HBMEC invasion.

The pathogenicity of microbes may be determined by substances sequestered from blood and bound to their constituent lipid. The brain may not perceive substances sequestered by microbes, to interfere with control to maintain normal levels. Pathological conditions can be induced as organisms exposed to antimicrobial substances/conditions and/or deprived of nutrients essential to cell wall synthesis, disintegrate to free lipid-bound compounds and produce L-forms that can deplete nutrients as they revert to bacteria. Microbes may act as active carriers for the continuing interaction of sequestered substances. Changes in the molecular structure of substances effected during sequesteration could cause them to be seen as substances 'synthesized' by an organism. In media that contain substances to inhibit 'contaminants', L-forms can be seen as mycoplasma. Elementary bodies of L-forms with a specific substance or tissue affinity may be seen as 'receptors'. Bartonella are global agents for disease--pleomorphic organisms (description suits Proteus)--and they can be seen as 'contaminants'.

Cat scratch disease is usually a self-limited illness associated with tender lymph nodes, fever, malaise, and fatigue. Lymphadenopathy usually resolves spontaneously within three to four months. Cat scratch disease can be atypical as indicated by the presentation of our patient.

University of Virginia, Department of Pediatrics, Charlottesville, Virginia, USA.

We describe 6 school-aged patients who presented with status epilepticus (SE) secondary to cat-scratch disease (CSD) encephalopathy to alert clinicians to this distinctive clinical entity. The hospital database for admissions during 1 year was reviewed for patients presenting with SE; 4 of 5 previously healthy school-aged children with SE had CSD encephalopathy based on elevated indirect fluorescent antibody titers to Bartonella henselae. CSD encephalopathy should be included in the differential diagnosis of school-aged children presenting with SE.

Department of Radiology, Royal Alexandra Hospital for Children, Sydney, Australia.

CT and MR imaging of the brain and gallium-67 scintigraphy showed an enhancing, gallium-avid mass in the left middle cranial fossa of a 10-year-old girl. Craniotomy revealed an inflammatory mass related to the left trigeminal nerve. The lesion contained rodlike bacteria, and serologic tests were positive for cat-scratch disease. Neurologic involvement in cat-scratch disease is uncommon, and the presence of organisms in neural tissue has not been reported.

We present a case of cat-scratch disease in a 9-year-old girl, complicated by encephalopathy and seizures. Bartonella (formerly Rochalimaea) henselae is the causative agent in cat-scratch disease; methods now available for detection of this pleomorphic, gram-negative bacterium, including polymerase chain reaction amplification and indirect fluorescence antibody testing, may lead to changes in standard criteria used to verify a diagnosis of cat-scratch disease.

Bartonella, genus Proteus, can cause immunodepressive disease. The organisms, in parasitized red blood cells, may invade the brain and every other system and space in the human body. Bartonella henselae is proposed to have a role in the pathogenesis of acquired immunodeficiency syndrome (AIDS) encephalopathy. Bartonella bacilliformis produces two known toxins that can induce spasm and angiomatosis, respectively, and manifest as diseases associated with symptomatic AIDS. The skin lesions of bartonellosis may be mistaken clinically and histologically for Kaposi's sarcoma. Bacteria of the genus Proteus produce L-forms: their elementary bodies may be mistaken for what are called the 'human immunodeficiency viruses' (HIV). Antibiotics, especially penicillin, induce bacteria to produce L-forms. Air pollution and high sugar, salt and fat diets are factors that may increase the lipid content of microbes that produce toxins and L-forms that may persist or revert to bacterial form.

Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

Bartonella (Rochalimaea) henselae causes cat-scratch disease, bacillary angiomatosis, peliosis hepatis, and fever in humans. B. henselae can be difficult to culture axenically, and as many as 5 weeks may be required before colonies are visible. We compared how different methods of blood collection and handling affect isolation of this pathogen. Blood specimens from B. henselae-infected cats were collected in both EDTA and Isolator blood-lysis tubes and were subsequently plated onto rabbit blood-brain heart infusion agar by using three different schedules: plating immediately, plating after 24 h at 25 degrees C, and plating after 26 days at -65 degrees C. Colonies were counted 14 and 35 days after plating. Blood collected in tubes containing EDTA, frozen at -65 degrees C, and then plated on blood agar yielded a median of 60,000 CFU/ml, compared with 25,333 CFU/ml after collection in the Isolator tubes (P < 0.01). Frozen blood yielded the largest number of B. henselae colonies for any of the schedules tested. These results support previous observations that the Isolator system is more sensitive than tubes containing EDTA for isolation of B. henselae and suggest that, for cat blood, collection in tubes containing EDTA and subsequent freezing may further improve the sensitivity of detection of B. henselae.

Recent reports of fastidious pathogens suggest the need for special blood cultures for immunocompromised patients. Blood cultures from 45 human immunodeficiency virus (HIV)-infected patients with unexplained fever (> or = 38.0 degrees C) and CD4 counts of < 125 cells per mm3 were collected into a vacuum tube with sodium polyanetholsulfonate, an Isolator tube, and BACTEC aerobic and anaerobic bottles. Blood from the sodium polyanethosulfonate tube was inoculated into BACTEC 13A bottles, which were read weekly for 16 weeks. Isolator sediment was divided among eight agar media, including four sheep blood agar media: chocolate agar, brain heart infusion blood agar, heart infusion blood agar, and brucella blood agar. Other agar plates included Sabouraud's, buffered charcoal-yeast extract, Middlebrook 7H11 (M7H11) with hemoglobin, and M7H11 with mycobactin J. Incubation conditions included air and CO2-enriched aerobic, microaerophilic, and anaerobic atmospheres. Aerobic BACTEC broths received an acridine orange stain on day 8 and were subcultured at 2, 4, and 8 weeks. Anaerobic BACTEC bottles were subcultured at 4 weeks. All solid media, including subcultures, were incubated for 8 weeks, providing a total of 16 weeks of incubation for each specimen. Clinically significant isolates included eight Mycobacterium avium complex isolates and one each of Bartonella henselae, Bartonella quintana, Shigella flexneri, Klebsiella oxytoca, and Cryptococcus neoformans. All isolates were detected with commercially available media and, with the exception of Bartonella spp., were recovered within incubation times routinely used in most clinical laboratories.

Bartonella bacilliformis invades the endothelial lining of the cardiovascular system. Damage to the red blood cells and white blood cells, the effects of the toxins, invasion of the brain and electrical charges induced by the organism so interfering with normal electrical stimulation of the heart may explain many of the features of cardiovascular disease (1-5).